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Abstract

Background: Variability in the onset of platelet inhibitory effects induced by oral P2Y12 receptor antagonists, including prasugrel and ticagrelor, has been shown in high-risk settings, underscoring the need for intravenous P2Y12 agents, such as cangrelor, characterized by immediate effects. To date there are no studies comparing the pharmacodynamic (PD) effects induced by cangrelor between ticagrelor and prasugrel-treated patients, which represented the aim of this investigation.

Methods: In a setting of a prospective randomized study, in vitro cangrelor effects were investigated in coronary artery disease (CAD) patients on maintenance aspirin (81mg/qd) and clopidogrel (75mg/qd) therapy, who then were switched to prasugrel or ticagrelor. Patients (n=110) were randomized to prasugrel (60mg LD/10mg MD qd) or ticagrelor (180mg LD/90mg MD bid) for 1 week. PD assessments, using the platelet reactivity index (PRI) by VASP, were performed before and after in vitro incubation with cangrelor (500 nM) during the acute (baseline, 30 min, 2 hrs) and chronic (1 week) phases of treatment.

Results:In vitro cangrelor significantly reduced PRI values irrespective of oral P2Y12 receptor inhibitor, with absolute changes more marked at baseline, while on clopidogrel, compared with prasugrel and ticagrelor. After switching to prasugrel or ticagrelor, in vitro cangrelor significantly reduced PRI values at all timepoints in both groups, with the exception of ticagrelor 2 hrs after LD (Fig. A and B). Overall, there were no differences in cangrelor induced antiplatelet effects between prasugrel and ticagrelor with PRI levels consistently low and similar at each time point (Fig. C).

Conclusions: In CAD patients treated with oral P2Y12 receptor inhibitors, in vitro cangrelor is associated with promptly enhanced platelet inhibition with similar effects in both prasugrel and ticagrelor treated patients during the acute and chronic phases of treatment.